PNPLA3 rs738409C/G polymorphism in cirrhosis: relationship with the aetiology of liver disease and hepatocellular carcinoma occurrence

Abstract

The PNPLA3 rs738409 C>G polymorphism is associated with cirrhosis. In synergy with gender, this polymorphism is a strong predictor of HCC occurrence among patients with cirrhosis.

Letter: PNPLA3 and alcoholic liver disease - an alert to methodological limitations

“…I voice concerns, however, over the approach taken to pooling the association data currently available. Not only do the numbers given differ from those previously published, 2,3 with regard to the majority of studies consulted, the authors could not possibly tell whether the at risk-allele was meant to be 'C' or rather 'G', as genetic exposure was not specified in the original articles. [3][4][5][6][7][8] For differentiation of the two alleles, DNA strand information is essential if the 'G' allele is not to be mistaken for the 'C' allele and vice versa.…”

Association of PNPLA3 Polymorphism with Hepatocellular Carcinoma Development and Prognosis in Viral and Non-Viral Chronic Liver Diseases

“…Interestingly, although PNPLA3 polymorphism has been related to hepatic steatosis in patients with HCV infection, its association with HCC development is less clear with conflicting results. Some studies have demonstrated that the GG genotype effect the risk of HCC development (Falleti et al, 2011;Sato et al, 2014), while most other studies have reported no such association (Nischalke et al, 2011;Guyot et al, 2013;Friedrich et al, 2014). For patients with HBV infection, recent data reported that PNPLA3 polymorphism was independently associated with hepatic steatosis, but not with advanced fibrosis and HCC development (Vigano et al, 2013;Brouwer et al, 2015;Zampino et al, 2015).…”

PNPLA3 gene in liver diseases

“…Indeed, only two small-sample case-control studies from Italy [32,61] initially reported a positive association between rs738409[G] and HCC in HCV-infected patients, while at least 2 others did not observe this result [55,56]. Moreover, results obtained from meta-analyses of these studies did not provide firm conclusions [16,53].…”

“…In alcoholic cirrhotic patients, the level of evidence is solid. All initial case-control studies conducted in this population reported significant associations with PNPLA3 variants, with ORs indicating increased risk [55][56][57][58]. Most studies in this field were conducted in Europe and included a homogeneous population of nearly 1,500…”